Fluorinated aromatic compounds are known useful starting materials for the manufacture of dyes, pharmaceuticals, agricultural chemicals and polymeric coating materials.
For example, 2-fluoronitrobenzene is an intermediate in the preparation of certain known herbicides; 1,3-difluorobenzene is used to prepare the anti-inflammatory agent "Difunisal" and the insecticide "Dibenzuron"; and 1,2 and 1,4-difluorobenzene are used in the preparation of other pharmaceutically active agents.
Heretofore, fluorinated aromatic compounds have been prepared by reaction of an appropriately substituted aromatic non-fluoro halo- or nitro- compound with an alkali metal fluoride, generally and most advantageously in the presence of an aprotic polar organic solvent. Representative and typical of such solvent-based processes are those disclosed in the following: U.S. Pat. No. 4,069,262 discloses preparing 2-fluoronitrobenzene by reacting 2-chloronitrobenzene with ultra-fine particulate KF in tetramethylenesulfone (sulfolane) containing a macrocyclic ether, i.e., "crown" ether, or a quaternary ammonium halide as catalyst.
U.S. Pat. No. 4,418,229 discloses the production of fluoronitrobenzenes by reacting appropriately substituted chloronitrobenzenes with an alkali metal fluoride at elevated temperatures, in an aprotic, polar organic solvent and a quaternary ammonium salt as phase-transfer catalyst, the quaternary salt being added incrementally during the course of the reaction inasmuch as such catalyst tends to be destroyed at the elevated temperatures employed. The solvents include dimethyl sulfoxide, sulfolane, bis(2-methoxyethyl ether), bis[2-(2-methoxyethoxy)ethyl]ether, hexamethylphosporamide, N-methylpyrrolidinone and dimethylformamide.
U.S. Pat. No. 4,229,365 discloses the preparation of substituted fluorobenzenes bearing nitro or cyano groups, and optionally alkyl or halo groups by reacting an appropriately substituted chlorobenzene with potassium fluoride in the presence of cesium fluoride as catalyst and an N,N-disubstituted carboxylic acid amide, nitrobenzene, nitrile, aliphatic sulfone and/or sulfoxide as the solvent.
U.S. Pat. No. 4,847,442 discloses a multi-step process for preparing 1,3-difluorobenzene which involves (a) halogen exchange fluorination of 2,4- or 2,6-dichlorobenzoyl chloride to the corresponding difluorobenzoyl fluoride by reaction with KF in a solvent in a first step. Solvents employed include amides such as dimethylformamide and N-methylpyrrolidinone, sulfoxides such as dimethyl sulfoxide and sulfones such as sulfolane.
European Patent 354,444/'90A2 discloses the production of fluorinated aromatic compounds by nucleophilic exchange of halo or nitro groups with KF in the presence of a phase transfer catalyst, a salt of a metal of Groups 3 to 5, of the Periodic Table, and preferably a solvent such as "dimethyl sulfoxide, N-methylpyrrolidone, tetramethylsulfone, benzonitrile, nitrobenzene, dimethylacetamide, ethylene glycol dimethyl ether or diglyme".
European Patent Application 0371 563/A2 discloses the preparation of chlorofluoro- and difluorobenzenes in the presence of CsF in a polar aprotic solvent under substantially anhydrous conditions. Suitable aprotic solvents disclosed are N-methylpyrrolidinone, N-cyclohexylpyrrolidinone, 1,3-dimethyl-2-imidazolidinone and 1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H)-pyrimidone.
The prior art processes suffer several disadvantages that add to the cost of assembling and carrying out a viable commercial process. These include the required use of such expedients as: ultra-fine particulate alkali metal fluoride; high-cost ("crown") ethers in an attempt to provide a more reactive "free" fluoride during the course of the reaction; phase-transfer catalysts and the apparent need to control their addition to the reaction medium in view of their tendency to be fugitive at the high temperatures of the halogen exchange replacement reaction; extraneous salt additives, and, most importantly, an aprotic polar solvent medium for the reaction, a requirement common to substantially all the art.
Not only are such solvents relatively expensive, but their use requires facilities for storing, transporting, handling, recovering and purifying them, as well as for preventing their escape into and contaminating the environment. All these expedients add significantly to the investment and operating costs for any process requiring their use.
It is well-known in the art [see, for example, Zoltewicz, Top. Curr. Chem. 59, 33-64 (1975) and Bunnett and Zahler, Chem. Revs. 49, 273-412 (1951)] that nucleophilic exchange in aromatic systems normally requires that the aromatic ring be activated by the presence of an appropriately positioned electron-withdrawing substituent. An important advantage of this invention is that ring activation is not required for substitution to occur.
It is also known, as disclosed by Brown, et al., Journal of Fluorine Chemistry, 30, 251-258 (1985), that tetraphenylphosphonium hydrogen difluoride, (C.sub.6 H.sub.5).sub.4 PHF.sub.2, can fluorinate organic substrates via halogen exchange or fluorodenitration reactions in the presence or absence of solvents. The phosphonium compound, however, suffer the disadvantage that it is much too expensive for commercial use.